Center for the "Development of a Virtual Tumor ('CViT')". Due to the inherent non-linearity and complexity of the many networked physiological processes involved on the cellular level alone, conventional reductionism-driven approaches fail if one plans to investigate how for example genetic mutations affect multicellular behavior or how spatial-temporal patterns of angiogenesis impact the efficacy of cancer therapies. Given the multi-scaled pathophysiology involved, it is becoming abundantly clear that cancer research requires a complex systems science approach. This P20 planning grant application brings together a multi-institutional, interdisciplinary group of investigators with track records in either the biomedical or the computational aspects of cancer research, or both. The goals for the Exploratory P20 phase are as follows: (AIM 1) to first establish an efficient infrastructure and workflow between the multiple teams, (AIM 2) to then collect, classify and archive the already developed modeling tools and techniques (i.e., building a digital model repository), and finally, (AIM 3) to initiate a pilot project, which connects and integrates three distinct modeling modules and platforms in order to test the hypothesis that molecular heterogeneity can quantitatively affect multicellular patterns. To accomplish these goals over the proposed three years, the team is structured into three cores: A) the administrative core, B) the computational modeling core (responsible for algorithm development and design of the digital model repository), and C) the biomedical data core (responsible for data collection and evaluation). The administrative core is guiding the ambitious effort and as such also responsible for organizing workshops and for seeking affiliations with educational and training programs as well as with other academic, governmental or corporate biomedical informatics groups and initiatives ('outreach and dissemination'). Anticipated success in this exploratory P20 phase during Year 1 and 2 will position CViT uniquely for a P50 Center application in its Year 3. The long term goal of CViT's P50 phase is to develop a generic tool-kit for modeling and simulating selected cancer types of interest such as breast, brain cancer, and melanoma following a paradigm-shifting cross-disciplinary complex systems approach. Combined with cutting edge biomedical data, this modeling tool-kit will allow cancer researchers to properly study cancer initiation and such critically linked progression features as invasion, angiogenesis and metastasis in the context of an emergent system. Ultimately, this module-based tool-kit will have important clinical applications including virtual trials and patient outcome predictions.